• Molecules and Cells
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• v.41 no.7
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• pp.653-664
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• 2018

The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

• Investigative Magnetic Resonance Imaging
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• v.12 no.2
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• pp.178-187
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• 2008

Purpose : To evaluate and compare the diagnostic accuracy of MRI and ultrasound(US) for estimation of invasion depth of gastric carcinoma by correlation with histopathologic findings in vitro and to find out the best MR pulse sequence for detection and accurate delineation of tumor. Materials and Methods : Resected specimen of total or subtotal gastrectomy from 53 patients with gastric carcinoma were done of imaging studies of MRI and US. And US was examined by using high frequency linear transducer for tumor invasion depth by a radiologist. In each case, both imaging findings of MRI and US were evaluated independently for tumor detection and invasion depth by consensus of two radiologists and were compared the diagnostic accuracy between two imaging modalities according to the histopathologic findings. MR imaging with five MR pulse sequences, spin echo T1 and in- and out-of phase gradient echo T1 weighted images, FSE and SSFSE T2 weighted images, were performed. Five MR pulse sequences were evaluated and compared on the point of detection and accurate distinction of tumor from surrounding normal tissue. Results : In EGC, diagnostic accuracy of US(77%) was superior than that of MRI(59%) but no statistically significant difference was noted between two imaging modalities(p=0.096). In AGC, both imaging modalities of MRI and US showed relatively high diagnostic accuracy as 97% and 84% respectively. Diagnostic accuracy of MRI was statistically better than that of US at the significant level(p<0.001). The best MR pulse sequence among five in each specimen was FSE T2WI(75.5%, 40/53) in both EGC and AGC. In AGC, FSE T2WI showed excellent imaging quality by showing very high ratio (93.5%, 29/31) of accurate delineation of tumor. Conclusion : MRI and US show relatively high diagnostic accuracy in the evaluation of tumor invasion depth of resected specimen in AGC. The most excellent pulse sequence of MRI for the evaluation of tumor invasion depth is FSE T2WI on the point of detection and accurate delineation of tumor in both EGC and AGC.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.417-425
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• 2017

Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.129-138
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• 2023

Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haploinsufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.399-409
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• 2009

Objectives : The aim of this study was to experiment the antitumor activity of Agrimonia pilosa Ledebour (APL) in human stomach cancer (AGS) cell lines (in vitro) and male C57BL/6J mouse (in vivo). Methods : The effects of the ethanol extract from the plant on several transplantable rodent tumors were investigated in vitro by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. DNA content analysis and Western blot analysis. Agrimonia pilosa Ledebour (APL) was given to rats with Lewis Lung Carcinoma (LLC) cells. The experimental rats were divided into 3 groups in vivo. Saline was injected into the abdominal cavity in the first group, 50 mg/kg APL was injected into the abdominal cavity in the second group and 100 mg/kg was injected into the abdominal cavity in the third group. After that, we checked their tumor volume periodically. Results : At first, human gastric cancer (AGS) cell lines (in vitro) showed decreased cell viability, and increased $sub-G_1$ contents. When we experimented rat intestinal epithelial (RIE)l as same condition, this result didn't show. With this, compared to normal cells, Agrimonia pilosa Ledebour (APL) led selectively to the extinction of cells only in human gastric cancer. Moreover, we showed that the traditional herbal medicine APL induced caspase-dependent apoptosis in AGS cells. Next, APL inhibited the growth of LLC-bearing mouse tumor. However, we could not verify APL induced caspase-dependent apoptosis in LLC-bearing mouse tumor. Conclusions : The roots of Agrimonia pilosa Ledebour (APL) contain some antitumor constituents.

• Korean journal of food and cookery science
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• v.20 no.4
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• pp.365-370
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• 2004

The study was carried out to evaluate the radical scavenging activity, and antimutagenic and anticancer effects in Korean soybean paste(doenjang) added with various mushrooms. Ganoderma lucidum doenjang(Gl-TD) showed significant inhibitory activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, with an IC$\sub$50/ value of 245$\mu\textrm{g}$/$m\ell$. In contrast, the other doenjang varieties appeared to have weaker antioxidant activity. Four kinds of doenjang didn't have any antimutagenic activity against N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) by adding of 5mg/plate, but exhibited a strong inhibitory effect(55∼70%) against aflatoxin B$_1$(AFB$_1$). Especially Phellinus linteus doenjang(Pl-TD) inhibited more than 70% of the mutagenicity induced by AFB$_1$ in Salmonella typhimurium TA100. On the other hand, the mushroom doenjang varieties showed relatively weak activity toward MNNG in SOS chromotest, their inhibitory rate ranging from 23% to 33%. Methanol extracts of Gl-TD and Pl-TD inhibited by 91∼92% the growth of AGS gastric cancer cells in a concentration of 100$\mu\textrm{g}$/$m\ell$.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.1 no.1
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• pp.19-35
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• 1994

To test the effectiveness of the preparatory audiovisual information with videotape, 34 patients with gastric cancer and who have scheduled for subtotal gastrectomy were studied with quasiexperimental research design. The subjects were selected from the 4 general surgical wards of one university hospital in Seoul, and assigned to experimental and control group conveniently. The videotaped information on the preparation and recovery for surgery was showed to the experimental subjects once before having operation. Data on the sleep and the state anxiety level before and after treatment day was collected with VSH sleep scale and STAI. The data was analyzed with t-test to test the effect of preparatory information and the Pearson's correlation to identify the correlation between anxiety and sleep. The results were summerized as follows : 1. After receiving the preparatory information, the level of anxiety of the experimental group was the same level as the initial, whereas that of the control group showed markedly increase. However no significant difference in anxiety between the two groups was found. 2. There was significant difference in sleep score between the experimental and the control group. 3. There was significant negative correlation between the state anxiety score and the sleep score. Based upon the above findings, this study concludes that preparatory information is effective to enhance sleep just prior to the surgery.

• Journal of Korean Neurosurgical Society
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• v.50 no.1
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• pp.60-63
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• 2011

Seizure is a foreseeable risk in patients with brain lesion. However, seizure during treating non-brain lesion is not a familiar situation to neurosurgeon. Posterior reversible encephalopathy syndrome (PRES) is a relatively common situation after systemic chemotherapy. The aim of this study is to make neurosurgeons aware of this potential medical problem. A 52-year-old woman with advanced gastric cancer, presented with low back pain due to spinal metastasis at the 4th lumbar vertebra. Ten cycles of chemotherapy with FOLFOX (5-Fluoruracil/Oxaliplatin) had been completed 23 days ago. Two days before the planned operation, a generalized tonic clonic seizure occurred. She did not have a history of hypertension or seizure. The seizure was stopped with lorazepam 4mg. The brain magnetic resonance (MR) imaging showed high signal changes in both parieto-occipital lobes on the T2-weighted images, and these were partially enhanced, suggesting PRES. The surgery was preceded by treatment with an antiepileptic drug. The MR images, taken 1.5 months after the seizure, showed that the lesion was no longer present. At 3 month follow-up, no additional seizure attack occurred without any seizure medication. The possibility of a seizure attack should be considered if the patient has a history of chemotherapy.

• Microbiology and Biotechnology Letters
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• v.50 no.2
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• pp.301-309
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• 2022

Helicobacter pylori (H. pylori) establishes infection in the human gastric mucosa for a long time and causes severe gastric diseases such as peptic ulcer and gastric cancer. When H. pylori is exposed to the antibacterial agents or inhibitors, the expression of pathogenic associated genes could be altered. In this study, we analyzed the transcriptional changes of H. pylori genes induced by zerumbone treatment. RNA expression changes were analyzed using next-generation sequencing (NGS), and then reverse transcription-polymerase chain reaction (RT-PCR) was performed to verify the results. As a result of NGS analysis, a total of 23 out of 1,632 genes were differentially expressed by zerumbone treatment. RT-PCR confirmed that zerumbone treatment regulated the expression level of 14 genes. Among the genes associated with DNA replication, transcription, virulence factors and T4SS components, 10 genes (dnaE, dnaQ, rpoA, rpoD, secA, flgE, flhA, virB5, virB8 and virB9) were significantly down-regulated and 4 genes (flaA, flaB, virB4 and virD4) were up-regulated. The results of our current study imply that zerumbone might be a potential therapeutic agent for H. pylori infection by regulating factors related to various H. pylori pathogenicity.